Neurotoxins from the venoms of two species of scorpion have been purified and characterized. Voltage clamp studies show that purified Centruroides sculpturatus neurotoxins selectively alter the voltage dependence of sodium activation. Neurotoxins obtaind from the venom of Leiurus quinquestratus selectively inhibit sodium inactivation. Purified radiolabeled neurotoxins from these two venoms demontrate high affinity saturable binding both to intact excitable membrane and to detergent solubilized membrane components. Leiurus neurotoxins display a Kd for this interaction near 5 x 10 to the minus 10th power M with a dissociation half time of several hours. Because of the physiological specificity of these neurotoxins we assume this to be binding to the inactivation or "h" gating components of voltage dependent sodium channel. Centruroides neurotoxins show quantitatively similar binding to presumptive activation or "m" gating components. Expriments will be performed to further characterize the specific binding of these toxins. A major question to be addressed is whether these two physiologically distinct toxins bind to a common membrane component or to molecularly distinct components. If the presumptive gating particles are distinct the relative stoichiometry of these elements will be determined. Cross competition studies will be carried out monitoring binding both to sites in intact membrane and to extracted membrane components. In subsequent work the scorpion neurotoxins will be employed as immobilized ligands in affinity chromatography procedures to isolate the presumptive "m" and "h" gating elements. A preliminary biochemical chracterization of these components will be carried out.